A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts

R. Mazzieri, F. Furlan, S. D'Alessio, E. Zonari, F. Talotta, P. Verde, F. Blasi

Research output: Contribution to journalArticle

Abstract

In addition to its role in invasion and metastasis of several tumors, the multifunctional urokinase receptor uPAR (urokinase plasminogen activator receptor) is directly involved in the growth of several cancer cells in vitro and in vivo. We have compared growth rate and oncogenic transformation in wild-type (wt) or uPAR-/- mouse embryonic fibroblasts (MEFs). Surprisingly, uPAR-/- MEFs grew faster than wt MEFs. This agreed with elevated levels of cell cycle mediators like extracellular signal-regulated protein kinase, p38, AP1 and Cyclin D1. Infection with a uPAR retrovirus reverted the effect, decreasing the growth rate.When MEFs were transformed with H-RasV12 and E1A oncogenes, the efficiency of transformation in uPAR-/- MEFs was higher than in wt. UPAR-/- MEFs grew faster at low serum, produced more colonies in agar and produced tumors in vivo in nude mice with a lower latency period. The properties of the heterozygous uPAR+/- MEFs were always intermediate. We conclude therefore that in MEFs uPAR concentration controls cell proliferation and the transforming activity of some oncogenes.

Original languageEnglish
Pages (from-to)725-732
Number of pages8
JournalOncogene
Volume26
Issue number5
DOIs
Publication statusPublished - Feb 1 2007

Fingerprint

Urokinase Plasminogen Activator Receptors
Fibroblasts
Growth
Oncogenes
Neoplasms
Cyclin D1
Extracellular Signal-Regulated MAP Kinases
Urokinase-Type Plasminogen Activator
Retroviridae
Nude Mice
Protein Kinases
Agar
Cell Cycle
Cell Proliferation
Neoplasm Metastasis

Keywords

  • Cell proliferation
  • E1A
  • Ink4a
  • Ras
  • Urokinase receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts. / Mazzieri, R.; Furlan, F.; D'Alessio, S.; Zonari, E.; Talotta, F.; Verde, P.; Blasi, F.

In: Oncogene, Vol. 26, No. 5, 01.02.2007, p. 725-732.

Research output: Contribution to journalArticle

Mazzieri, R. ; Furlan, F. ; D'Alessio, S. ; Zonari, E. ; Talotta, F. ; Verde, P. ; Blasi, F. / A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts. In: Oncogene. 2007 ; Vol. 26, No. 5. pp. 725-732.
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